Drugs used in treatment of mental illness affect the uptake, storage, release or metabolism of catecholamines. Evidence from this, as well as other laboratories, indicates that such drugs, e.g., reserpine, Li ion, L-DOPA as well as other compounds which affect catecholamines in the CNS, such as 6-hydroxydopamine or alpha methyl-p-tyrosine also alter the metabolism of amino acids, e.g., glutamic acid, aspartic acid, glutamine and GABA in the CNS. Since monoamines increase levels of cyclic AMP in neurons and glia and cyclic AMP can affect energy metabolism it is probable that interactions between catecholamine and amino acid metabolism may be mediated in part by cyclic AMP. This latter concept will be investigated in this proposal. The rat will be the experimental animal. Slices prepared from the caudate nucleus or cerebral cortex will be incubated in the presence of norepinephrine or dopamine, their agonists (isoproterenol, apormorphine) or antagonists (propanolol, fluphenazine, haloperidol) or combinations of agonist and antagonist. The changes in levels of cyclic AMP will be measured and the turnover of the amino acids followed by labelling with radioactive glucose and acetate. In in vivo experiments chronic lesions will be produced in the rat substantia nigra by stereotoxic injections of 6-hydroxydopamine. Turnover of amino acids in the caudate nucleus of the lesioned and non-lesioned sides will be followed by i.p. injection of radioactive glucose and acetate. The effect of administered apormorphine or amphetamine on the labelling pattern of the amino acids will also be studied.